Following stroke, changes in neuronal connectivity in tissue surrounding the infarct play an important role in both spontaneous recovery of neurological function and in treatment-induced improvements in function. Microglia and astrocytes influence this process through direct interactions with the neurons and as major determinants of the local tissue environment. Subpopulations of peri-infarct glia proliferate early after stroke providing a possible target to modify recovery. Treatment with cell cycle inhibitors can reduce infarct volume and improve functional recovery. However, it is not known whether these inhibitors can influence neurological function or alter the responses of peri-infarct glia without reducing infarction. The present study aimed to address these issues by testing the effects of the cell cycle inhibitor, olomoucine, on recovery and peri-infarct changes following photothrombotic stroke. Stroke was induced by photothrombosis in the forelimb sensorimotor cortex in Sprague-Dawley rats. Olomoucine was administered at 1 h and 24 h after stroke induction. Forelimb function was monitored up to 29 days. The effects of olomoucine on glial cell responses in peri-infarct tissue were evaluated using immunohistochemistry and Western blotting. Olomoucine treatment did not significantly affect maximal infarct volume. Recovery of the affected forelimb on a placing test was impaired in olomoucine-treated rats, whereas recovery in a skilled reaching test was substantially improved. Olomoucine treatment produced small changes in aspects of Iba1 immunolabelling and in the number of CD68-positive cells in cerebral cortex but did not selectively modify responses in peri-infarct tissue. The content of the astrocytic protein, vimentin, was reduced by 30% in the region of the lesion in olomoucine-treated rats. Olomoucine treatment modified functional recovery in the absence of significant changes in infarct volume. The effects on recovery were markedly test dependent, adding to evidence that skilled tasks requiring specific training and general measures of motor function can be differentially modified by some interventions. The altered recovery was not associated with specific changes in key responses of peri-infarct microglia, even though these cells were considered a likely target for early olomoucine treatment. Changes detected in peri-infarct reactive astrogliosis could contribute to the altered patterns of functional recovery.

中文翻译：

---

细胞周期抑制剂 olomoucine 对大鼠光血栓性中风后功能恢复和梗死周围小胶质细胞和星形胶质细胞反应的不同影响

中风后，梗塞周围组织中神经元连接的变化在神经功能的自发恢复和治疗诱导的功能改善中起重要作用。小胶质细胞和星形胶质细胞通过与神经元的直接相互作用以及作为局部组织环境的主要决定因素来影响这一过程。梗死周围神经胶质亚群在中风后早期增殖，为改善恢复提供了可能的目标。用细胞周期抑制剂治疗可以减少梗死体积并改善功能恢复。然而，尚不清楚这些抑制剂是否可以影响神经功能或改变梗塞周围神经胶质的反应而不减少梗塞。本研究旨在通过测试细胞周期抑制剂奥洛穆辛的作用来解决这些问题，光血栓性卒中后的恢复和梗死周围变化。中风是由 Sprague-Dawley 大鼠前肢感觉运动皮层的光血栓形成引起的。在中风诱导后 1 小时和 24 小时给予奥洛穆辛。监测前肢功能长达 29 天。使用免疫组织化学和蛋白质印迹法评估了 olomoucine 对梗塞周围组织中神经胶质细胞反应的影响。Olomoucine 治疗对最大梗死体积没有显着影响。在 olomoucine 治疗的大鼠中，在放置测试中受影响的前肢的恢复受损，而在熟练的伸手测试中的恢复得到了显着改善。Olomoucine 治疗在 Iba1 免疫标记和大脑皮层 CD68 阳性细胞数量方面产生了微小变化，但没有选择性地改变梗死周围组织的反应。在 olomoucine 治疗的大鼠中，病变区域的星形细胞蛋白波形蛋白的含量减少了 30%。在梗塞体积没有显着变化的情况下，奥洛穆辛治疗改善了功能恢复。对恢复的影响明显依赖于测试，这增加了证据表明，需要特定训练的熟练任务和运动功能的一般测量可以通过一些干预措施进行不同的修改。改变的恢复与梗塞周围小胶质细胞的关键反应的特定变化无关，尽管这些细胞被认为是早期 olomoucine 治疗的可能目标。